Rare eye cancer pathway uncovered

Scientists have uncovered the secret behind the rapid progression of retinoblastoma, a rare type of childhood eye cancer. Rather than being caused by a series of mutations, like most cancers, the loss of a single gene results in multiple other genes being switched on or off, triggering cancer. The findings allowed researchers to stop the cancer developing in mice.

Retinoblastoma develops in the retina, the light-sensing tissue at the back of the eye. It affects more than 5,000 children worldwide every year, many of them under the age of five.

Scientists already know that mutations in the RB1 gene cause the cancer, but the reason for this was unclear. They assumed that, like in other cancers, loss of RB1 allows lots of further mutations in other genes to occur, resulting in cancer.

But when the genomes of four retinoblastoma biopsies were sequenced, the researchers were amazed to find that there were no extra mutations in genes associated with cancer.Instead they found that molecular modifications had been made to a range of genes with the result that they were either switched off or sent into overdrive.

This explains why the cancer develops so quickly – because genes can be turned on and off faster than mutations would occur. One gene that they identified as being overactive was SYK, which has previously been linked to other forms of cancer. When retinoblastomas in mice were treated with a compound that blocked the activity of SYK, the cancerous cells died.

Work is now underway to develop the experimental compound, called R406, into a treatment that can be delivered directly to the affected eye.

For more information on retinobastoma research, please see the AnimalResearch.info page on blindness.